tbuckley/cabot-search huggingface dataset:
Patient mortality following new‐onset heart failure stratified by cancer type and status
Authors: Nina Nouhravesh, Jarl E. Strange, Anders Holt, Jacob Tønnesen, Camilla Fuchs Andersen, Sebastian K. Nielsen, Lars Køber, Robert J. Mentz, Dorte Nielsen, Emil L. Fosbøl, Morten Lamberts, Morten Schou
Journal: European Journal of Heart Failure (2023)

Expected 1-year survival is essential to risk stratification of patients with heart failure (HF); however, little is known about the 1-year prognosis of patients with HF and cancer. Thus, the objective was to investigate the 1-year prognosis following new-onset HF stratified by cancer status in patients with breast, gastrointestinal, or lung cancer.All Danish patients with new-onset HF from 2000 to 2018 were included. Cancer status was categorized as history of cancer (no cancer-related contact within 5 years of HF diagnosis), non-active cancer (curative intended procedure administered) and active cancer. Standardized 1-year all-cause mortality was reported using G-computation. Age-stratified 1-year all-cause mortality was estimated using the Kaplan-Meier estimator. In total, 193 359 patients with HF were included, 7.3% had either a breast, gastrointestinal, or lung cancer diagnosis. Patients with cancer were older and more comorbid than patients without cancer. Standardized 1-year all-cause mortality (95% confidence intervals) was 24.6% (23.0-26.2%), 27.1% (25.5-28.6%), and 29.9% (25.9-34.0%) for history of breast, gastrointestinal and lung cancer, respectively, which was comparable to patients with non-active cancers. For active breast, gastrointestinal and lung cancer, standardized 1-year all-cause mortality was 36.2% (33.8-38.6%), 49.0% (47.2-50.9%), and 61.6% (59.7-63.5%), respectively. One-year all-cause mortality increased incrementally with age, except for active lung cancer.Standardized 1-year all-cause mortality was comparable for patients with history of cancer and non-active cancer regardless of cancer type, but varied comprehensively for active cancers. Prognostic impact of age was limited for active lung cancer. Thus, granular stratification of cancer is necessary for optimized management of new-onset HF.
Tmem178 Negatively Regulates <scp>IL</scp>‐1β Production Through Inhibition of the <scp>NLRP3</scp> Inflammasome
Authors: Kunjan Khanna, Hui Yan, Muneshwar Mehra, Nidhi Rohatgi, Gabriel Mbalaviele, Elizabeth D. Mellins, Roberta Faccio
Journal: Arthritis & Rheumatology (2023)

Inflammasomes modulate the release of bioactive interleukin (IL)-1β. Excessive IL-1β levels are detected in patients with systemic juvenile idiopathic arthritis (sJIA) and cytokine storm syndrome (CSS) with mutated and unmutated inflammasome components, raising questions on the mechanisms of IL-1β regulation in these disorders.
Treatment Response in First-Line Metastatic Pancreatic Ductal Adenocarcinoma Is Stratified By a Composite Index of Tumor Proliferation and CD8 T-Cell Infiltration
Authors: Gregory L. Beatty, Devora Delman, Jiayi Yu, Mingen Liu, Joey H. Li, Liti Zhang, Jae W. Lee, Renee B. Chang, Nathan Bahary, Eugene P. Kennedy, Andrea Wang-Gillam, Gabriela R. Rossi, Ignacio Garrido-Laguna
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Determinants of treatment outcomes to chemotherapy-based regimens in metastatic pancreatic ductal adenocarcinoma (PDA) remain ill-defined. Our aim was to examine tissue-based correlates of treatment response and resistance using matched baseline and on-treatment biopsies collected from patients with PDA treated in the first-line metastatic setting. Experimental Design: Patients with treatment-naïve metastatic PDA were enrolled in a Phase II trial (NCT02077881) investigating gemcitabine plus nab-paclitaxel in combination with indoximod, an orally administered small-molecule inhibitor of the IDO pathway. Baseline and on-treatment biopsies (week 8) of metastatic lesions (88% liver) were collected from a cohort of responders (N = 8) and non-responders (N = 8) based on RECIST v1.1 and examined by multiplex IHC and mRNA sequencing. Results: Treatment altered the transcriptional profile of metastatic lesions with a decrease in tumor cell proliferation independent of treatment response. The antiproliferative response was seen in both basal and classical PDA subtypes. PDA subtype was not associated with survival outcomes; instead, genes involved in immune activation distinguished responders from non-responders. Tumor response was associated with an increase in CD3+ and CD8+ T-cell infiltrates into metastatic lesions. A composite of decreased tumor proliferation in response to treatment and increased CD8 T-cell infiltration in metastatic lesions identified responders and associated with a favorable survival outcome. Conclusions: Our findings suggest that inhibiting cancer cell proliferation alone in PDA is insufficient to produce tumor responses and support a role for tumor-extrinsic mechanisms, such as CD8+ T cells, which combine with the cancer cell proliferation index to define treatment outcomes.
Cycles
Authors: Michael J. Slade
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Mortality among patients with diffuse large B-cell lymphoma and mental disorders: a population-based study
Authors: Inna Y Gong, Matthew C Cheung, Kelvin K W Chan, Sumedha Arya, Neil Faught, Andrew Calzavara, Ning Liu, Oreofe O Odejide, Gregory Abel, Paul Kurdyak, Michael J Raphael, Thomas Kuczmarski, Anca Prica, Lee Mozessohn
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Mental disorders have been reported in patients with diffuse large B-cell lymphoma (DLBCL), but studies examining their association with mortality are lacking. Methods We conducted a population-based study using linked administrative health-care databases from Ontario, Canada. All patients with DLBCL 18 years of age or older treated with rituximab-based therapy between January 1, 2005, and December 31, 2017, were identified and followed until March 1, 2020. Mental disorders were defined as either preexisting or postdiagnosis (after lymphoma treatment initiation). Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) between mental disorders and 1-year and all-cause mortality while controlling for covariates. Results We identified 10 299 patients with DLBCL. The median age of the cohort was 67 years; 46% of patients were female, and 28% had a preexisting mental disorder. At 1-year follow-up, 892 (9%) had a postdiagnosis mental disorder, and a total of 2008 (20%) patients died. Preexisting mental disorders were not associated with 1-year mortality (adjusted HR = 1.06, 95% confidence interval [CI] = 0.96 to 1.17, P = .25), but postdiagnosis disorders were (adjusted HR = 1.51, 95% CI = 1.26 to 1.82, P = .0001). During a median follow-up of 5.2 years, 2111 (22%) patients had a postdiagnosis mental disorder, and 4084 (40%) patients died. Both preexisting and postdiagnosis mental disorders were associated with worse all-cause mortality (preexisting adjusted HR = 1.12, 95% CI = 1.04 to 1.20, P = .0024; postdiagnosis adjusted HR = 1.63, 95% CI = 1.49 to 1.79, P &amp;lt; .0001). Conclusions Patients with DLBCL and mental disorders had worse short-term and long-term mortality, particularly those with postdiagnosis mental disorders. Further studies are needed to examine mental health service utilization and factors mediating the relationship between mental disorders and inferior mortality.
The safety and efficacy between remimazolam and propofol in intravenous anesthesia of endoscopy operation: a systematic review and meta-analysis
Authors: Mei-ji Zhao, Hai-feng Hu, Xin-lei Li, Xiao-ming Li, Da-chuan Wang, Ming-jie Kuang
Journal: International Journal of Surgery (2023)

Background: Propofol is the most widely used intravenous anesthetic in endoscopic surgery, but is associated with several adverse reactions. Public research has shown that remimazolam, a safe general anesthetic, is increasingly being used as a substitute for propofol in clinical operations. Our meta-analysis aimed to analyze whether the adverse reaction rate of remimazolam in endoscopic surgery is acceptable and whether the surgical success rate is not lower than that of propofol. Aim: This meta-analysis examined the adverse events and efficacy of remimazolam vs. propofol during endoscopic surgery. Method: MEDLINE, EMBASE, ClinicalTrials.gov, and Google Scholar were comprehensively searched. Seven studies comparing remimazolam and propofol were included in our meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Cochrane manual were used to assess the quality of the results published in all included studies to ensure that our meta-analysis results are reliable and worthwhile. Results: Compared to propofol, the use of remimazolam reduced postoperative injection pain [Relative Risk (RR)=0.06, 95% confidence interval (CI): 0.03–0.12, P &lt;0.00001], postoperative hypotension (RR=0.45, 95% CI: 0.28–0.73, P =0.001), and postoperative respiratory depression (RR=0.20, 95% CI: 0.08–0.47, P =0.0002); however, it also slightly reduced the success rate of the operation [Risk Difference (RD)=−0.02, 95% CI: −0.04–−0.01, P =0.0007]. There were no significant differences in the occurrence of bradycardia symptoms after the operation (RD=−0.01, 95% CI: −0.03–0.01, P =0.35), recovery time after the operation [STD Mean Difference (SMD)=0.68, 95% CI: −0.43–1.80, P =0.23] or discharge time (SMD=0.17, 95% CI: −0.58–0.23, P =0.41). We also performed a subgroup analysis of each corresponding outcome. Conclusion: Our analysis showed that remimazolam may be a safer shock option than propofol for endoscopic surgery. However, further research is required to determine their utility.
Moujalled DM, Brown FC, Chua CC, et al. Acquired mutations in BAX confer resistance to BH3-mimetic therapy in acute myeloid leukemia. <i>Blood</i>. 2023;141(6):634-644.
Journal: Blood (2023)

In Figure 4D on page 642, both instances of "BAX -/-" in the legend for the graph should read "BAK -/-."In the description of panel B in the legend, the range of concentrations of idarubicin should be 0.0001 to 1 μM, not 0.001 to 1 μM.The corrected Figure 4 and legend are shown below.
Urinary Tumor DNA MRD Analysis to Identify Responders to Neoadjuvant Immunotherapy in Muscle-invasive Bladder Cancer
Authors: Ruiyun Zhang, Jingyu Zang, Di Jin, Feng Xie, Akezhouli Shahatiaili, Guangyu Wu, Lu Zhang, Lu Wang, Yue Zhang, Zhixin Zhao, Pan Du, Shidong Jia, Jinhai Fan, Guanglei Zhuang, Haige Chen
Journal: Clinical Cancer Research (2023)

Bladder preservation is a viable option for some patients with muscle-invasive bladder cancer (MIBC), but an effective noninvasive biomarker test to accurately identify promising candidates is lacking. Here we present the clinical application of a novel tissue-agnostic, urine-based minimal residual disease (MRD) assay in the neoadjuvant setting for personalized disease surveillance and actionable target identification to facilitate bladder-sparing treatment approaches.The urinary tumor DNA (utDNA) analysis was evaluated in an investigator-initiated phase I trial RJBLC-I2N003 in which 20 patients diagnosed with resectable MIBC were treated presurgically with the PD-1 inhibitor toripalimab followed by radical cystectomy (RC).We showed that neoadjuvant toripalimab therapy was feasible, safe, and induced a 40% rate (8/20) of pathologic complete response. Longitudinal utDNA profiling outperformed radiographic assessment and conventional biomarkers to predict the pathologic outcome of immune checkpoint blockade. In addition to detecting 3 exceptional responders with molecular MRD-negative status, we identified 7 other individuals characterized for utDNA response and 4 harboring FGFR3 mutants, all of whom (60%, 12/20) could have postponed or avoided RC.These findings demonstrate the safety and efficacy of neoadjuvant toripalimab, and suggest the immense potential of noninvasive utDNA MRD testing to guide tailored decision-making with regard to bladder preservation and change the current treatment paradigm for patients with MIBC.
Red blood cell-mimicking liposomes loading curcumin promote diabetic wound healing
Authors: Qinghan Tang, Mei Dong, Zeyu Xu, Nannan Xue, Ruihan Jiang, Xuchao Wei, Jingyue Gu, Yue Li, Rongshuang Xin, Jia Wang, Xueying Xiao, Xin Zhou, Shaoping Yin, Yiwei Wang, Jun Chen
Journal: Journal of Controlled Release (2023)
Lipid nanoparticles for siRNA delivery in cancer treatment
Authors: Souhaila H. El Moukhtari, Elisa Garbayo, Ane Amundarain, Simón Pascual-Gil, Arantxa Carrasco-León, Felipe Prosper, Xabier Agirre, María J. Blanco-Prieto
Journal: Journal of Controlled Release (2023)
Microwave-activated Cu-doped zirconium metal-organic framework for a highly effective combination of microwave dynamic and thermal therapy
Authors: Yifu Feng, Qian Chen, Chong Jin, Yanyun Ruan, Qi Chen, Weidong Lin, Chumeng Zhu, Tinglin Zhang, Yang Zhang, Jie Gao, Jinggang Mo
Journal: Journal of Controlled Release (2023)
Rural and urban exposures shape early life immune development in South African children with atopic dermatitis and <scp>nonallergic</scp> children
Authors: Nonhlanhla Lunjani, Anoop T. Ambikan, Carol Hlela, Michael Levin, Avumile Mankahla, Jeannette I. Heldstab‐Kast, Tadech Boonpiyathad, Ge Tan, Can Altunbulakli, Clive Gray, Kari C. Nadeau, Ujjwal Neogi, Cezmi A. Akdis, Liam O'Mahony
Journal: Allergy (2023)

Abstract Background Immunological traits and functions have been consistently associated with environmental exposures and are thought to shape allergic disease susceptibility and protection. In particular, specific exposures in early life may have more significant effects on the developing immune system, with potentially long‐term impacts. Methods We performed RNA‐Seq on peripheral blood mononuclear cells (PBMCs) from 150 children with atopic dermatitis and healthy nonallergic children in rural and urban settings from the same ethnolinguistic AmaXhosa background in South Africa. We measured environmental exposures using questionnaires. Results A distinct PBMC gene expression pattern was observed in those children with atopic dermatitis (132 differentially expressed genes [DEGs]). However, the predominant influences on the immune cell transcriptome were related to early life exposures including animals, time outdoors, and types of cooking and heating fuels. Sample clustering revealed two rural groups (Rural_1 and Rural_2) that separated from the urban group (3413 and 2647 DEGs, respectively). The most significantly regulated pathways in Rural_1 children were related to innate activation of the immune system (e.g., TLR and cytokine signaling), changes in lymphocyte polarization (e.g., TH17 cells), and immune cell metabolism (i.e., oxidative phosphorylation). The Rural_2 group displayed evidence for ongoing lymphocyte activation (e.g., T cell receptor signaling), with changes in immune cell survival and proliferation (e.g., mTOR signaling, insulin signaling). Conclusions This study highlights the importance of the exposome on immune development in early life and identifies potentially protective (e.g., animal) exposures and potentially detrimental (e.g., pollutant) exposures that impact key immunological pathways.
High-resolution bioenergetics correlates the length of continuous protonatable diaminoethane motif of four-armed oligo(ethanamino)amide transfectants to cytotoxicity
Authors: Arnaldur Hall, Jiri Bartek, Ernst Wagner, Ulrich Lächelt, Seyed Moein Moghimi
Journal: Journal of Controlled Release (2023)

Recent clinical success with Onpattro and cationic ionizable lipid nanoparticle-based mRNA vaccines has rejuvenated research in the design and engineering of broader synthetic cationic vectors for nucleic acid compaction and transfection. However, perturbation of metabolic processes and cytotoxicity are still of concern with synthetic cationic vectors. Here, through an integrated bioenergetic and biomembrane integrity probing in three different human cell lines we reveal the dynamic effect of a library of sequence-defined four-arm oligo(ethanamino)amide transfectant on cell homeostasis, and identify metabolically safe building units over wide concentration ranges. The results show differential effects of the oligo(ethanamino)amide structure of comparable molecular weight on cell energetics. The severity of polycation effect on bioenergetic crisis follows with the length of continuous protonatable diaminoethane motif in the ascending order of glutaryl-triethylene tetramine, succinyl-tetraethylene pentamine and succinyl-pentaethylene hexamine. We further identify oligomeric structures that do not induce bioenergetic crisis even at high concentrations. Finally, transfection studies with a library of polyplexes carrying a reporter gene show no correlation between transfection efficiency and cytotoxicity. These observations demonstrate the usefulness of integrated high-resolution respirometry and plasma membrane integrity probing as a highly sensitive medium-throughput screening strategy for identification and selection of safe building units for transfectant engineering.
Women in STEM becoming independent: Embracing every experience as part of the learning process
Authors: Lucie Van Emmenis
Journal: The Journal of Experimental Medicine (2023)

In this Viewpoint, we hear from a cross section of women, across multiple research fields, discussing their science and the process of setting up a lab as an independent researcher. As well as being able to celebrate the positives of becoming an independent researcher, we would also like to use this platform to discuss the unique challenges they face as women scientists in their respective scientific environments.
4D printing of biodegradable elastomers with tailorable thermal response at physiological temperature
Authors: N. Paunović, D. Meyer, A. Krivitsky, A.R. Studart, Y. Bao, J.-C. Leroux
Journal: Journal of Controlled Release (2023)

4D printing has a great potential for the manufacturing of soft robotics and medical devices. The alliance of digital light processing (DLP) 3D printing and novel shape-memory photopolymers allows for the fabrication of smart 4D-printed medical devices in high resolution and with tailorable functionalities. However, most of the reported 4D-printed materials are nondegradable, which limits their clinical applications. On the other hand, 4D printing of biodegradable shape-memory elastomers is highly challenging, especially when transition points close to physiological temperature and shape fixation under ambient conditions are required. Here, we report the 4D printing of biodegradable shape-memory elastomers with tailorable transition points covering physiological temperature, by using poly(D,L-lactide-co-trimethylene carbonate) methacrylates at various monomer feed ratios. After the programming step, the high-resolution DLP printed stents preserved their folded shape at room temperature, and showed efficient shape recovery at 37 °C. The materials were cytocompatible and readily degradable under physiological conditions. Furthermore, drug-loaded devices with tuneable release kinetics were realized by DLP-printing with resins containing polymers and levofloxacin or nintedanib. This study offers a new perspective for the development of next-generation 4D-printed medical devices.
Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction: The CAMEO-DAPA Trial
Authors: Barry A. Borlaug, Yogesh N.V. Reddy, Amanda Braun, Hidemi Sorimachi, Massar Omar, Dejana Popovic, Alessio Alogna, Michael D. Jensen, Rickey Carter
Journal: Circulation (2023)

Sodium-glucose cotransporter-2 inhibitors reduce risk of hospitalization for heart failure in patients who have heart failure with preserved ejection fraction (HFpEF), but the hemodynamic mechanisms underlying these benefits remain unclear. This study sought to determine whether treatment with dapagliflozin affects pulmonary capillary wedge pressure (PCWP) at rest and during exercise in patients with HFpEF.
CD4+ TIL to the Rescue of Anti–PD-1 Failure by Targeting MHC-II
Authors: Allison Betof Warner, Jason J. Luke
Journal: Clinical Cancer Research (2023)

Summary In this CCR Translations, we discuss the potential for tumor-infiltrating lymphocyte therapy to overcome immune checkpoint inhibitor resistance through CD4+-mediated and MHC-II–dependent killing. Validating these results from human tumors has potential to improve the clinical application of adoptive cellular transfer in advanced cancers. See related article by Draghi et al., p. 3937
Scarlett McNally: Let’s focus on tertiary prevention and perioperative care
Authors: Scarlett McNally
Journal: BMJ (2023)

We've known for millennia that prevention is better than cure.An excellent new report, A Covenant for Health, 1 which involved input from across the political spectrum along with the King's Fund, defines where to act to improve health: nutrition, exercise, pollution, smoking, alcohol, and promotion of mental health.
Anatomical characteristics of the alveolar process and basal bone that have an effect on socket healing
Authors: Maurício G. Araújo, Debora R. Dias, Flavia Matarazzo
Journal: Periodontology 2000 (2023)

Abstract Following tooth extraction, a sequence of events takes place in order to close the wound and restore tissue homeostasis, a process called socket healing. The outcome of socket healing includes a marked reduction of the ridge dimensions. The amount of tissue loss that occurs during healing is influenced by several local and systemic factors. Thus, the aim of the present review was to describe the effect of anatomical characteristics of the alveolar process and basal bone on the socket healing outcome. The studies included showed that the quantity (number) and quality (composition) of socket walls exhibited a significant influence on the ridge diminution. A damaged socket (3 walls or less), as well as a thin buccal bone wall, which quickly resorbs negatively affected the healing outcome. Periodontally compromised sockets appeared to promote more extensive dimensional changes. Angulation between tooth and basal bone in addition to basal bone dimensions may also have altered the wound environment and influenced socket healing. The findings from the present review suggest that some anatomical characteristics of the alveolar process and basal bone have an effect on socket healing.